Association of donor hepatectomy time with liver transplantation outcomes: A multicenter retrospective study.

BACKGROUND: Prolonged donor hepatectomy time may be implicated in early and late complications of liver transplantation. AIM: To evaluate the impact of donor hepatectomy time on outcomes of liver transplant recipients, mainly early allograft dysfunction. METHODS: This multicenter retrospective study included brain-dead donors and adult liver graft recipients. Donor-recipient matching was obtained through a crossover list. Clinical and laboratory data were recorded for both donors and recipients. Donor hepatectomy, cold ischemia, and warm ischemia times were recorded. Primary outcome was early allograft dysfunction. Secondary outcomes included need for retransplantation, length of intensive care unit and hospital stay, and patient and graft survival at 12 months. RESULTS: From January 2019 to December 2021, a total of 243 patients underwent a liver transplant from a brain-dead donor. Of these, 57 (25%) developed early allograft dysfunction. The median donor hepatectomy time was 29 (23-40) min. Patients with early allograft dysfunction had a median hepatectomy time of 25 (22-38) min, whereas those without it had a median time of 30 (24-40) min (P = 0.126). CONCLUSION: Donor hepatectomy time was not associated with early allograft dysfunction, graft survival, or patient survival following liver transplantation.

Glycated albumin in the detection of diabetes during COVID-19 hospitalization.

BACKGROUND: Diabetes has emerged as an important risk factor for COVID-19 adverse outcomes during hospitalization. We investigated whether the measurement of glycated albumin (GA) may be useful in detecting newly diagnosed diabetes during COVID-19 hospitalization. METHODS: In this cross-sectional test accuracy study we evaluated HCPA Biobank data and samples from consecutive in-patients, from 30 March 2020 to 20 December 2020. ROC curves were used to analyse the performance of GA to detect newly diagnosed diabetes (patients without a previous diagnosis of diabetes and admission HbA1c ≥6.5%). RESULTS: A total of 184 adults (age 58.6 ± 16.6years) were enrolled, including 31 with newly diagnosed diabetes. GA presented AUCs of 0.739 (95% CI 0.642-0.948) to detect newly diagnosed diabetes. The GA cut-offs of 19.0% was adequate to identify newly diagnosed diabetes with high specificity (85.0%) but low sensitivity (48.4%). CONCLUSIONS: GA showed good performance to identify newly diagnosed diabetes and may be useful for identifying adults with the condition in COVID-19-related hospitalization.

Ultra-Processed Food Consumption, Poorer Nutritional Quality, and Lower Muscle Mass in Immediate and Late Postkidney Transplant Periods.

OBJECTIVE: To assess the consumption of ultra-processed foods (UPFs) in the immediate (2 months after transplantation) and late post-transplant (14 months after transplantation) periods among kidney transplant patients and to examine its correlation with nutritional quality and body composition. DESIGN AND METHODS: A cross-sectional analysis of 96 kidney transplant recipients divided into 2 groups: immediate post-transplant (n = 71) and late post-transplant (n = 25). Sociodemographic, anthropometric, and laboratory data were collected and grouped in a database. Food intake was evaluated by a validated food frequency questionnaire and foods were divided according to the NOVA classification system. The consumption of UPFs was calculated and statistical analyses were performed to evaluate its correlation with nutritional components and body composition. RESULTS: The consumption of UPFs was 649.4 [420.0-1061.72] kcal/day, accounting for 33.3 ± 11.9% of the total daily energy intake. The immediate post-transplant group showed higher total daily energy and UPFs intake compared to the late post-transplant group (P = .002 and P = .046, respectively), although the energy contribution of UPFs was similar between both groups. UPFs intake was positively correlated with higher percentages of total fat, trans fat, saturated, monounsaturated fat, polyunsaturated fat, starch, and sodium (P < .05 for all analyses). An inverse correlation was observed between UPFs consumption and the percentage of protein and carbohydrates in the food intake (P = .025 and P = .008, respectively). In the immediate post-transplant group, a higher intake of UPFs was correlated with lower muscle mass (r = -0.250, P = .037). CONCLUSIONS: The findings of this study reveal a pattern of increased consumption of UPFs among kidney transplant patients in comparison to the national average. This higher intake of UPFs was correlated with lower nutritional quality during both periods. Moreover, a significant correlation was observed between UPFs consumption and adverse body composition parameters, specifically in the immediate post-transplant period.

Does liraglutide alleviate inflammation in brain-dead donors? A randomized clinical trial.

Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1ß, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic ( BCL2 ), endoplasmic reticulum stress markers ( DDIT3/CHOP , HSPA5/BIP ), and antioxidant ( superoxide dismutase 2 , uncoupling protein 2 ) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (-28 [-182, 135] vs. 32 [-10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (-0.01 [-2.2, 1.5] vs. 1.9 [-0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2-8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

Early retinal neurovascular findings in post-transplant diabetes mellitus patients without clinical signs of diabetic retinopathy.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a specific subtype of diabetes with an uncertain impact on mortality and morbidity in post-transplant patients. Diabetic retinopathy is the most common microvascular complication of diabetes mellitus, but the long-term clinical progression in PTDM is unknown. New technologies are being used to assess pre-clinical signs of retinal changes, such as swept-source optical coherence tomography (OCT) and OCT-angiography. The aim of this study was to detect pre-clinical structural and vascular changes in the retina using swept-source-OCT and OCT-angiography in patients with PTDM. METHODS: In this retrospective cohort study, post-kidney transplant patients were divided into PTDM and non-PTDM (control) groups. Both eyes of eligible PTDM patients and controls were included in this study. Inner retinal layer thickness was measured with swept-source-OCT. Retinal capillary density and the foveal avascular zone were measured with OCT-angiography. RESULTS: In the PTDM group, reduced thickness was found in the inferior ganglion cell layer plus inner plexiform layer (95% CI -8.76 to -0.68; p = 0.022) and the temporal inferior segment (95% CI -10.23 to -0.76; p = 0.024) of the inner retina, as well as in the retinal nerve fiber layer in the temporal (95% CI -34.78 to -9.28 p = 0.001) and temporal inferior segments (95% CI -33.26 to -5.03 p = 0.008). No significant differences were found in the vascular capillary plexus between groups at all depths, segments, or foveal avascular zone (p = 0.088). CONCLUSIONS: According to OCT-angiography, PTDM patients had reduced inner neurosensory retinal layers but no significant change in vascular density, which suggests that early neuroretinal degeneration might occur prior to vascular changes secondary to PTDM. Prospective studies could help elucidate the clinical course of retinal neuropathy and microvascular pathology in PTDM and provide a better understanding of PTDM complications.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Laughter as medicine: A systematic review and meta-analysis of interventional studies evaluating the impact of spontaneous laughter on cortisol levels.

OBJECTIVES: Laughter as an expression of humor has been recognized as good medicine for centuries. The health benefits of humor-induced well-being remain unclear and thus we conducted a systematic review and meta-analysis of interventional studies to evaluate the impact of spontaneous laughter on stress response as measured by cortisol levels. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE/PubMed, EMBASE, PsycINFO, Scopus, and Clinicaltrials.gov. ELIGIBILITY CRITERIA: Interventional studies, which could be either randomized placebo-controlled trials (RCTs) or quasi-experimental studies, conducted in adults that compared any spontaneous laughter intervention to a controlled setting and reported changes in cortisol levels were selected. DATA EXTRACTION AND SYNTHESIS: We examined the impact of laughter on percentage change in cortisol levels by calculating pooled estimates of the absolute differences between arithmetic means before and after interventions as compared to control using random-effects model. RESULTS: Eight studies (315 participants; mean age 38.6) met our inclusion criteria; four were RCTs and four were quasi-experiment studies. Five studies evaluated the impact of watching a humor/comedy video, two studies evaluating laughter sessions administered by a trained laughter therapist, and one study evaluating a self-administered laughter program. Pooling these data showed a significant reduction in cortisol levels by 31.9% (95%CI -47.7% to -16.3%) induced by laughter intervention compared to control group with no evidence of publication bias (P = 0.66). Sensitivity analyses demonstrated that even a single laughter session induced a significant reduction of 36.7% in cortisol (95%CI -52.5% to -20.8%). In addition, analyses including the four RCTs reinforced these results by demonstrating a significant reduction in cortisol levels promoted by laughter as compared to the placebo arm [-37.2% (95%CI -56.3% to -18.1%)]. CONCLUSIONS: Current evidence demonstrates that spontaneous laughter is associated with greater reduction in cortisol levels as compared with usual activities, suggesting laughter as a potential adjunctive medical therapy to improve well-being. TRIAL REGISTRATION: Registration number: CRD42021267972.

What is Known About Dietary Interventions and Body Weight Management After Kidney Transplantation? A Scoping Review.

OBJECTIVE: Several studies report weight gain after kidney transplantation, which is commonly related to poor outcomes. However, recommendations for dietary interventions aiming to manage these patients' weight are still scarce in the literature. Thus, this review seeks to describe the state of literature on the effect of dietary interventions on weight after kidney transplantation. DESIGN: Scoping review. METHODS: This review was designed according to the recommendations for scoping reviews elaborated by the Joanna Briggs Institute. Studies assessing the effect of dietary interventions on body weight after kidney transplantations were searched in MEDLINE, EMBASE, and Clinicaltrials.gov databases up to June 28, 2021. Two independent reviewers summarized the data collected. RESULTS: Thirteen (503 patients) of the 4.983 articles identified in the searched databases were included in our study. Most studies were published before 2010 and presented incomplete methodology descriptions. Nutritional counseling and dietary prescriptions according to the Step 1 diet of the American Heart Association (AHA) were the most common interventions. Only 2 studies evaluated changes in body weight as primary outcome. Three studies were randomized clinical trials (RCT), and none of these found the adopted interventions to demonstrate benefits. CONCLUSION: Our scoping review evinced a scarcity of data available in the literature addressing this topic. Most studies were not controlled and presented poor methodological quality. Moreover, these studies included small sample sizes, so that the assessment of dietary interventions in these patients still lacks power for definitive conclusions. Prospective RCT should be conducted to define effective in preventing weight gain or weight loss after kidney transplant.

Elevated Extracellular HSP72 and Blunted Heat Shock Response in Severe COVID-19 Patients.

AIMS: We hypothesized that critically ill patients with SARS-CoV-2 infection and insulin resistance would present a reduced Heat Shock Response (HSR), which is a pathway involved in proteostasis and anti-inflammation, subsequently leading to worse outcomes and higher inflammation. In this work we aimed: (i) to measure the concentration of extracellular HSP72 (eHSP72) in patients with severe COVID-19 and in comparison with noninfected patients; (ii) to compare the HSR between critically ill patients with COVID-19 (with and without diabetes); and (iii) to compare the HSR in these patients with noninfected individuals. METHODS: Sixty critically ill adults with acute respiratory failure with SARS-CoV-2, with or without diabetes, were selected. Noninfected subjects were included for comparison (healthy, n = 19 and patients with diabetes, n = 22). Blood samples were collected to measure metabolism (glucose and HbA1c); oxidative stress (lypoperoxidation and carbonyls); cytokine profile (IL-10 and TNF); eHSP72; and the HSR (in vitro). RESULTS: Patients with severe COVID-19 presented higher plasma eHSP72 compared with healthy individuals and noninfected patients with diabetes. Despite the high level of plasma cytokines, no differences were found between critically ill patients with COVID-19 with or without diabetes. Critically ill patients, when compared to noninfected, presented a blunted HSR. Oxidative stress markers followed the same pattern. No differences in the HSR (extracellular/intracellular level) were found between critically ill patients, with or without diabetes. CONCLUSIONS: We demonstrated that patients with severe COVID-19 have elevated plasma eHSP72 and that their HSR is blunted, regardless of the presence of diabetes. These results might explain the uncontrolled inflammation and also provide insights on the increased risk in developing type 2 diabetes after SARS-CoV-2 infection.

Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis.

Although advanced age and presence of comorbidities significantly impact the variation observed in the clinical symptoms of COVID-19, it has been suggested that genetic variants may also be involved in the disease. Thus, the aim of this study was to perform a systematic review with meta-analysis of the literature to identify genetic polymorphisms that are likely to contribute to COVID-19 pathogenesis. Pubmed, Embase and GWAS Catalog repositories were systematically searched to retrieve articles that investigated associations between polymorphisms and COVID-19. For polymorphisms analyzed in 3 or more studies, pooled OR with 95% CI were calculated using random or fixed effect models in the Stata Software. Sixty-four eligible articles were included in this review. In total, 8 polymorphisms in 7 candidate genes and 74 alleles of the HLA loci were analyzed in 3 or more studies. The HLA-A*30 and CCR5 rs333Del alleles were associated with protection against COVID-19 infection, while the APOE rs429358C allele was associated with risk for this disease. Regarding COVID-19 severity, the HLA-A*33, ACE1 Ins, and TMPRSS2 rs12329760T alleles were associated with protection against severe forms, while the HLA-B*38, HLA-C*6, and ApoE rs429358C alleles were associated with risk for severe forms of COVID-19. In conclusion, polymorphisms in the ApoE, ACE1, TMPRSS2, CCR5, and HLA loci appear to be involved in the susceptibility to and/or severity of COVID-19.

Polymorphisms in ACE1, TMPRSS2, IFIH1, IFNAR2, and TYK2 Genes Are Associated with Worse Clinical Outcomes in COVID-19.

Although advanced age, male sex, and some comorbidities impact the clinical course of COVID-19, these factors only partially explain the inter-individual variability in disease severity. Some studies have shown that genetic polymorphisms contribute to COVID-19 severity; however, the results are inconclusive. Thus, we investigated the association between polymorphisms in ACE1, ACE2, DPP9, IFIH1, IFNAR2, IFNL4, TLR3, TMPRSS2, and TYK2 and the clinical course of COVID-19. A total of 694 patients with COVID-19 were categorized as: (1) ward inpatients (moderate symptoms) or patients admitted at the intensive care unit (ICU; severe symptoms); and (2) survivors or non-survivors. In females, the rs1990760/IFIH1 T/T genotype was associated with risk of ICU admission and death. Moreover, the rs1799752/ACE1 Ins and rs12329760/TMPRSS2 T alleles were associated with risk of ICU admission. In non-white patients, the rs2236757/IFNAR2 A/A genotype was associated with risk of ICU admission, while the rs1799752/ACE1 Ins/Ins genotype, rs2236757/IFNAR2 A/A genotype, and rs12329760/TMPRSS2 T allele were associated with risk of death. Moreover, some of the analyzed polymorphisms interact in the risk of worse COVID-19 outcomes. In conclusion, this study shows an association of rs1799752/ACE1, rs1990760/IFIH1, rs2236757/IFNAR2, rs12329760/TMPRSS2, and rs2304256/TYK2 polymorphisms with worse COVID-19 outcomes, especially among female and non-white patients.

Copeptin and stress-induced hyperglycemia in critically ill patients: A prospective study.

OBJECTIVES: Copeptin, an equimolar indicator of serum antidiuretic hormone levels, has been associated with higher mortality in critically ill patients and with the development of diabetes in the general population. The aim of the present study was to investigate the association of copeptin levels with glycemic parameters in critically ill patients and to compare the time-course of copeptin in survivors and non-survivors. DESIGN: Prospective cohort study. PATIENTS: From June to October 2019, critically ill patients were prospectively enrolled and followed for 90 days. MEASUREMENTS: Plasma copeptin levels were determined at intensive care unit (ICU) admission (copeptin T1), 24 h (copeptin T2), and 48 h (copeptin T3) after study entry. Blood glucose and glycated hemoglobin levels were measured. ICU, in-hospital, and 90-day mortality, and length of stay in the ICU and hospital were evaluated. RESULTS: 104 patients were included. No significant correlation was detected between copeptin levels and blood glucose (r = -0.17, p = 0.09), HbA1c (r = 0.01, p = 0.9), glycemic gap (r = -0.16, p = 0.11), and stress hyperglycemia ratio (r = -0.14, p = 0.16). Copeptin T3 levels were significantly higher in survivors than in non-survivors at hospital discharge (561 [370-856] vs 300 [231-693] pg/mL, p = 0.015) and at 90 days (571 [380-884] vs 300 [232-698] pg/mL, p = 0.03). CONCLUSIONS: No significant correlations were found between copeptin levels and glycemic parameters, suggesting that copeptin is not a relevant factor in the induction of hyperglycemia during critical illness. Copeptin levels at ICU day 3 were higher in survivors than in non-survivors.

All-cause mortality and cardiovascular safety of basal insulin treatment in patients with type 2 diabetes mellitus: A systematic review with meta-analysis and trial sequential analysis.

AIM: To evaluate the risk of all-cause and cardiovascular mortality, acute myocardial infarction, and stroke associated with insulin treatment in patients with type 2 diabetes. METHODS: A systematic review with meta-analysis of randomized clinical trials (RCTs) was performed. EMBASE, Cochrane, and PubMed databases were searched for RCTs reporting mortality or cardiovascular events and comparing basal insulin to any treatment in patients with type 2 diabetes. Data were summarized with Mantel-Haenzel relative risk (RR). Trial sequential analysis (TSA) was used to evaluate the reliability of the results considering a 20% relative risk difference between treatments. PROSPERO Registry: CRD42018087336. RESULTS: In total, 2351 references were identified, and 26 studies (24348 patients) were included. Most studies evaluated glargine insulin (69%), compared insulin to GLP-1 analogs (57%), and evaluated add-on therapy with metformin (77%). Insulin was not associated with increased all-cause mortality (RR 0.99; 95% confidence interval (CI) 0.92-1.06), cardiovascular mortality (RR 1.01; 95% CI 0.91-1.13), myocardial infarction (RR 1.02; 95% CI 0.92-1.15), or stroke (RR 0.87; 95% CI 0.68-1.12). Insulin treatment increased severe hypoglycemia risk (RR 2.98; 95% CI 2.47-3.61). All analyses had low statistical heterogeneity. TSA confirmed these findings: optimal sample size (myocardial infarction), futility boundary (all-cause mortality, cardiovascular mortality, and stroke) and harm boundary (hypoglycemia) were reached. CONCLUSION: Treatment with basal insulin of patients with type 2 diabetes does not increase the risk of cardiovascular events or death. Despite the increased risk of hypoglycemia, these findings reinforce that insulin is a safe option in the treatment of type 2 diabetes.

Decrease in Pancreatic Perfusion of Patients with Type 2 Diabetes Mellitus Detected by Perfusion Computed Tomography.

OBJECTIVES: The objectives of the study was to compare pancreatic perfusion by computed tomography in type 2 diabetes and non-diabetic subjects. MATERIAL AND METHODS: In this case-control study, 17 patients with type 2 diabetes and 22 non-diabetic controls were examined with a dynamic 192-slices perfusion computed tomography for estimating pancreatic perfusion parameters. RESULTS: Thirty-nine patients were included (22 with Type 2 diabetes mellitus [T2DM]), with a mean age of 64 years. There were significant differences in some pancreatic perfusion parameters in patients with and without type 2 diabetes. Blood volume (BV) was lower in pancreatic head (with T2DM: 14.0 ± 3.4 vs. without T2DM: 16.1 ± 2.4 mL/100 mL; P = 0.033), pancreatic tail (with: 14.4 ± 3.6 vs. without: 16.8 ± 2.5 mL/100 mL; P = 0.023), and in whole pancreas (with: 14.2 ± 3.2 vs. without: 16.2 ± 2.5 mL/100 mL; P = 0.042). Similar behavior was observed with mean transit time (MTT) in pancreatic head (with: 7.0 ± 1.0 vs. without: 7.9 ± 1.2 s; P = 0.018), pancreatic tail (with: 6.6 ± 1.3 vs. without: 7.7 ± 0.9 s; P = 0.005), and in whole pancreas (with: 6.8 ± 1.0 vs. without: 7.7 ± 0.9 s; P = 0.016). BV in head, tail, and whole pancreas had negative correlations with age (head r: -0.352, P = 0.032; tail r: -0.421, P = 0.031; whole pancreas r: -0.439, P = 0.007), and fasting plasma glucose (head r: -0.360, P = 0.031; tail r: -0.483, P = 0.003; whole pancreas r: -0.447, P = 0.006). In a multivariate linear regression model, HbA1c was independently associated with decrease in BV in whole pancreas (ß: -0.884; CI95%: -1.750 to -0.017; P = 0.046). CONCLUSION: Pancreatic BV and MTT were significantly lower in patients with type 2 diabetes. BV was decreased with older age and poorer glycemic control.

Risk factors associated with weight gain after kidney transplantation: A cohort study.

BACKGROUND: Renal transplantation is the best modality of renal replacement therapy for patients with end-stage renal disease. However, it is associated with weight gain and metabolic abnormalities, which adversely impact transplant outcomes. OBJECTIVE: The objective of this study was to identify the risk factors of one-year weight gain after renal transplantation. METHODS: A retrospective cohort study was conducted with 374 patients that underwent kidney transplantation between January 2006 and July 2013. Clinical and laboratory variables were collected from electronic records, and the outcome of interest was weight gain during the first year after renal transplantation. The data were reported as mean ± standard deviation, median (interquartile range) or number of subjects (%). The association between variables were assessed via chi-square test and ANOVA. For analysis of risk factors related to the outcomes of interest, multivariable logistic regression models were used. RESULTS: There were 181 (48.4%) female patients, 334 (89.3%) with white ethnicity and the mean age was 44.4 ± 12.8 years. The mean BMI pre-transplant was 24.7 ± 4.1 kg/m2, and 35 (9.9%) patients were classified as obese; 119 (33.6%) as overweight; 187 (52.8%) as normal weight; and 13 (3.7%) as malnourished. After one year of follow-up, the mean BMI was 26.2 ± 5.0 kg/m2, and 61 (17.3%) patients were classified as obese; 133 (37.8%) as overweight; 148 (42.0%) as normal weight; and 10 (2.8%) as malnourished. Weight gain was observed in 72.7% patients, and the average increase was 7.12 ± 5.9 kg. The female gender, lower pre-transplant body weight, lower number of hospitalizations, and a kidney received from a living donor were associated with weight gain by more than 5% in the first year post-transplant. CONCLUSION: Female gender and lower pre-transplant body weight were independently associated with weight gain by more than 5% in the first year after kidney transplantation; lower rates of hospitalization and donation from living donors were also risk factors for this outcome.

Plasma progranulin levels in obese patients before and after Roux-en-Y gastric bariatric surgery: a longitudinal study.

BACKGROUND: Bariatric surgery stands out as the most effective long-term intervention for sustainable weight loss and metabolic improvement in patients with severe obesity. Progranulin was recently identified as an adipokine related to obesity and inflammation, revealing a metabolic function and proinflammatory properties. OBJECTIVE: To evaluate plasma progranulin levels before and after 6 months of bariatric surgery in Roux-en-Y gastric bypass (RYGB). SETTING: Tertiary referral hospital, southern Brazil. METHODS: This was a prospective longitudinal study, including 23 obese patients who underwent RYGB. Demographic and clinical characteristics, body composition, and resting energy expenditure were evaluated. Plasma progranulin was determined with enzyme-linked immunosorbent assays in a peripheral blood sample collected before and 6 months after the surgical procedure. RESULTS: The participants were mostly women (78.3%), with a mean age of 42.3 ± 10.8 years and baseline body mass index of 48.8 ± 10.4 kg/m2. Regarding the anthropometric parameters, there were differences in the pre- and post-RYGB values, with reduction of weight, body mass index, body fat percentage, and cervical and abdominal circumferences. All laboratory parameters improved, such as lipid profile and fasting glycemia, and resting energy expenditure values decreased significantly. Plasma progranulin levels decreased from 47.6 ± 13.5 ng/mL before RYGB to 40.4 ± 9.9 ng/mL after 6 months of surgery (P = .005). The reduction of progranulin did not correlate with body composition or laboratory data. CONCLUSIONS: Plasma progranulin levels significantly reduced 6 months after RYGB, but it could not be explained by changes in anthropometry, body composition, or glycemic or lipid profile.

Metabolic effects of antihyperglycemic agents and mortality: meta-analysis of randomized controlled trials.

The effects of antihyperglycemic medications on cardiovascular events and mortality are heterogeneous and their effects on intermediate factors might explain these differences. This systematic review explores the relationship between metabolic factors, mechanism of action, and mortality effects of antihyperglycemic medications in type 2 diabetes. Randomized trials assessing the effects of antihyperglycemic medications on all-cause or cardiovascular mortality in type 2 diabetes were included. Myocardial infarction, stroke, and heart failure were secondary outcomes. The effects of medications on HbA1c, severe hypoglycemia (SH), body weight, systolic blood pressure (SBP), and mechanism of action were evaluated. Meta-analyses and meta-regressions were performed grouping studies according to the above-cited factors. All-cause mortality was lower for medications that reduced HbA1c, SH, body weight, and SBP. Decreased cardiovascular mortality was associated with lower HbA1c, SH, SBP. Myocardial infarction and stroke were also associated with favorable metabolic profile. These findings were not confirmed in meta-regression models. Medications associated with lower SH, body weight and SBP had a lower risk of heart failure. In conclusion, medications with better metabolic profile were associated with reduced all-cause and cardiovascular mortality. These findings are based on indirect comparisons and must be applied cautiously.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Hypoglycemia symptoms and awareness of hypoglycemia in type 1 diabetes mellitus: cross-cultural adaptation and validation of the Portuguese version of three questionnaires and evaluation of its risk factors.

BACKGROUND: To adapt and validate the Clarke and Gold questionnaires and the Edinburgh Hypoglycemia Symptom Scale (EHSS) to Brazilian Portuguese and to determine the prevalence and risk factors associated with impaired awareness of hypoglycemia (IAH) in patients with type 1 diabetes mellitus (T1DM). METHODS: The process of translation, cultural adaptation, and validation of the questionnaires followed the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)-Task Force for Translation and Cultural Adaptation. Patients with T1DM for a minimum of 12 months, aged 18 years or older, and with Brazilian nationality were selected to participate. RESULTS: A total of 123 patients were enrolled. The Clarke and Gold questionnaires as well as the EHSS exhibited adequate internal consistency, test-retest reliability, and convergent validity. The prevalence of IAH was 38.3% with the Clarke questionnaire and 25.2% with the Gold questionnaire. The prevalence increased with longer duration of diabetes, lower HbA1c, and lower eGFR. CONCLUSIONS: The validation and cross-cultural adaptation of the proposed questionnaires to Brazilian Portuguese were adequate. In this sample of T1DM, the prevalence of IAH was high and associated with a longer duration of T1DM, lower HbA1C and lower eGFR.

Brain death-induced cytokine release is not associated with primary graft dysfunction: a cohort study. / A liberação de citocinas induzida pela morte cerebral não está associada à disfunção primária do enxerto: um estudo de coorte.

OBJECTIVE: To examine the association between donor plasma cytokine levels and the development of primary graft dysfunction of organs transplanted from deceased donors. METHODS: Seventeen deceased donors and the respective 47 transplant recipients were prospectively included in the study. Recipients were divided into two groups: group 1, patients who developed primary graft dysfunction; and group 2, patients who did not develop primary graft dysfunction. Donor plasma levels of TNF, IL-6, IL-1ß, and IFN-γ assessed by ELISA were compared between groups. RESULTS: Sixty-nine organs were retrieved, and 48 transplants were performed. Donor plasma cytokine levels did not differ between groups (in pg/mL): TNF, group 1: 10.8 (4.3 - 30.8) versus group 2: 8.7 (4.1 - 33.1), p = 0.63; IL-6, group 1: 1617.8 (106.7 - 5361.7) versus group 2: 922.9 (161.7 - 5361.7), p = 0.56; IL-1ß, group 1: 0.1 (0.1 - 126.1) versus group 2: 0.1 (0.1 - 243.6), p = 0.60; and IFN-γ, group 1: 0.03 (0.02 - 0.2) versus group 2: 0.03 (0.02 - 0.1), p = 0.93). Similar findings were obtained when kidney transplants were analyzed separately. CONCLUSION: In this sample of transplant recipients, deceased donor plasma cytokines TNF, IL-6, IL-1ß, and IFN-γ were not associated with the development of primary graft dysfunction.

OBJETIVO: Examinar a associação entre os níveis de citocinas no plasma do doador e o desenvolvimento de disfunção primária do enxerto de órgãos transplantados a partir de doadores falecidos. MÉTODOS: Foram incluídos no estudo de forma prospectiva 17 doadores falecidos e os respectivos 47 pacientes receptores de transplante. Os receptores foram divididos em dois grupos: grupo 1, de pacientes que desenvolveram disfunção primária do enxerto, e grupo 2, de pacientes que não desenvolveram disfunção primária do enxerto. Os níveis de TNF, IL-6, IL-1ß, e IFN-γ, avaliados por meio de ELISA, foram comparados entre os grupos. RESULTADOS: Obtiveram-se 69 órgãos, sendo realizados 48 transplantes. Os níveis plasmáticos de citocinas nos doadores não diferiram entre os grupos (em pg/mL): TNF no grupo 1, com 10,8 (4,3 - 30,8) versus no grupo 2, com 8,7 (4,1 - 33,1), com valor de p = 0,63; IL-6 no grupo 1: 1.617,8 (106,7 - 5.361,7) versus no grupo 2: 922,9 (161,7 - 5.361,7), com p = 0,56; IL-1ß, no grupo 1: 0,1 (0,1 - 126,1) versus no grupo 2: 0,1 (0,1 - 243,6), com p = 0,60; e IFN-γ, no grupo 1: 0,03 (0,02 - 0,2) versus no grupo 2: 0,03 (0,02 - 0,1), p = 0,93). Obtivemos resultados similares ao examinar separadamente os casos de transplante renal. CONCLUSÃO: Nesta amostra de receptores de transplante, os níveis plasmáticos das citocinas TNF, IL-6, IL-1ß e IFN-γ nos doadores não se associaram com o desenvolvimento de disfunção primária do enxerto.